(Abstract) Despite the growing worldwide burden of dengue fever, the global economic impact of dengue illness is poorly documented. Using a common protocol, we present the first multicountry estimates of the direct and indirect costs of dengue cases in eight American and Asian countries. We conducted prospective studies of the cost of dengue in five countries in the Americas (Brazil, El Salvador, Guatemala, Panama, and Venezuela) and three countries in Asia (Cambodia, Malaysia, and Thailand). All studies followed the same core protocol with interviews and medical record reviews. Overall mean costs were I$514 and I$1,394 for an ambulatory and hospitalized case, respectively. With an annual average of 574,000 cases reported, the aggregate annual economic cost of dengue for the eight study countries is at least I$587 million. Preliminary adjustment for under-reporting could raise this total to $1.8 billion, and incorporating costs of dengue surveillance and vector control would raise the amount further. Dengue imposes substantial costs on both the health sector and the overall economy.
(Abstract) Dengue is a re-emerging arboviral disease of great public health importance. Limited understanding of protective immune responses against dengue has hampered advancement of dengue vaccine candidates. Demonstrating an immunological correlate of protection has been limited to associating quantitative neutralizing antibody titers with clinical outcomes following infection. There have been a number of studies investigating the role of cell mediated immunity (CMI) in natural infections and these have demonstrated roles in both virus clearance and potentiating disease. Vaccine developers have extended the exploratory study of CMI in natural infection to the study of dengue vaccine recipients.
(Abstract) We calculated disability adjusted life years (DALYs) lost to dengue per million individuals annually from 1986 through 2006. To calculate DALYs, we compiled data on the number of dengue cases by age, clinical syndrome and outcome. We evaluated the sensitivity of our results to multiplication factors used to adjust for inaccuracies in reporting using a Monte Carlo method. Assessment of dengue burden requires consideration of all clinical syndromes over multiple years. Our results indicate that the dengue burden is as high as the burden of other major infectious diseases that afflict the Brazilian population, including malaria. These results may prompt policy makers to elevate the prioritization of dengue control, and allocate resources needed to curtail the increasing dengue burden.
(Abstract) Preparations for dengue vaccine trials as well as vaccine introduction strategies require laboratory-based surveillance on an international and coordinated level. The Pediatric Dengue Vaccine Initiative (PDVI) has developed an international consortium of field sites in Latin America and Asia. These sites conduct community-based and enhanced passive laboratory-based surveillance of dengue fever. Through this consortium, PDVI is facilitating harmonized laboratory-based surveillance processes, so that disease incidence can be compared between different regions and countries. Prevention of dengue fever is the most suitable primary end point for a proof-of-concept dengue vaccine trial. However, such trials may provide insufficient information for stratified analysis of outcomes according to varied risk factors and virus serotype. Consequently large community-based demonstration trials may be necessary.
(Abstract) Guidelines for the clinical evaluation of dengue vaccines in endemic areas have recently been developed, building upon earlier recommendations published in 2002. This new document discusses the rationale and background of dengue vaccine trials and outlines dengue case definitions, proposed efficacy end points, requirements for trial sites, methods of measurement and proposed safety schedules. Demonstrated protective efficacy against each of the four dengue virus serotypes without safety concerns is the objective of any candidate tetravalent vaccine clinical trial. Accurate epidemiological data of dengue and other circulating flaviviruses over multiple transmission seasons are required to address factors such as background flavivirus immunity and subclinical infections that may confound serological results. Furthermore, bridging and post-licensure studies may be necessary to extend conclusions concerning vaccine characteristics, while co-administration trials are necessary in paediatrics. These guidelines are primarily aimed at national regulatory authorities, vaccine developers and research scientists and should be analysed, discussed and adjusted where necessary.
(Abstract) The re-emergence and subsequent failure to control dengue in Latin America provides a compelling illustration of the clinical, political and socio-economic challenges to eradicating dengue across the world. Insufficient political commitment, inadequate financial resources and increased urbanisation have contributed to the re-emergence and dramatic increase in dengue fever and dengue haemorrhagic fever in all 19 Latin American countries previously certified as free of Aedes aegypti. Successful introduction of a dengue vaccine will require an educational programme that clearly communicates the cost-effectiveness and desirability of this interventional measure.
(Abstract) We have reported the epidemic patterns of dengue disease in the Region of the Americas from 1980 through 2007. Dengue cases reported to the Pan American Health Organization were analyzed from three periods: 1980-1989 (80s), 1990-1999 (90s), and 2000-2007 (2000-7). Age distribution data were examined from Brazil, Venezuela, Honduras, and Mexico. The highest incidence was observed among adolescents and young adults; dengue hemorrhagic fever incidence was highest among infants in Venezuela. Increasing dengue morbidity/mortality was observed in the Americas in recent decades.
(Abstract) Dengue has been reportable in Cambodia since 1980. Virological surveillance began in 2000 and sentinel surveillance was established at six hospitals in 2001. Currently, national surveillance comprises passive and active data collection and reporting on hospitalized children aged 0–15 years. This report summarizes surveillance data collected since 1980.
(Abstract) Dengue virus is the most widespread geographically of the arboviruses and a major public health threat in the tropics and subtropics. Scientific advances in recent years have provided new insights about the pathogenesis of more severe disease and novel approaches into the development of antiviral compounds and dengue vaccines. The efforts to find specific dengue inhibitors are intensifying and the tools to evaluate the efficacy of new drugs are now in place for rapid translation into trials in humans. Furthermore, several dengue vaccine candidates are in development, of which the chimeric dengue/yellow fever vaccine has now entered phase 3 trials. Until the availability of a licensed vaccine, disease surveillance and vector population control remain the mainstay of dengue prevention.